Cell death pathways in dry eye disease: Insights into ocular surface inflammation

Dry eye disease (DED) is increasingly prevalent, with inflammation playing a crucial role in its pathogenesis. Severe cases of DED result in significant ocular discomfort and visual impairment due to damage and loss of ocular surface epithelial cells. The precise mechanisms underlying the loss of these epithelial cells remain a subject of ongoing research and debate. Programmed cell death (PCD) mechanisms, including pyroptosis, apoptosis, and necroptosis, are known to be critical in maintaining ocular surface homeostasis and responding to stressors in DED. The concept of PANoptosis, which integrates elements of various PCD pathways, has been implicated in the development of numerous systemic diseases, including infections, cancer, neurodegenerative, and inflammatory conditions. It also provides novel insights into the inflammatory processes underlying DED. This review highlights the crosstalk of PCD pathways in DED, particularly the significance of PANoptosis in ocular inflammation and its potential as a therapeutic target for more effective interventions.